Drug Incompatibilities Research Articles

Incompatible intravenous drug combinations and respective physician and nurse knowledge: a study in routine paediatric intensive care

ObjectivesTo identify incompatible intravenous drug combinations in routine paediatric intensive care and evaluate physician and nurse knowledge.MethodsIn a university paediatric intensive care unit, intravenous drug incompatibilities were analysed using a...

Polypharmacy and enteral nutrition in patients with complex chronic diseases

Oral medications are often administered through enteral feeding tubes in patients with complex chronic diseases. It is important to consider possible interactions between drugs and enteral nutrition that might lead to unsuccessful treatment or tube occlusion. These patients become subjects for higher risk of problems and errors such as drug incompatibility with enteral nutrition and inappropriate dosage form selection. It is possible to minimize the risk of tube occlusion and incompatibilities problems by recognizing potential medication errors, selecting the most appropriate drug and dosage form and using appropriate administration techniques. In this context, high-alert medications for patients with chronic diseases deserve special attention. Furthermore, risk exposure should be considered among healthcare professionals and patient caregivers handling hazardous drugs. Therefore, main incompatibility problems between drugs and enteral nutrition have been reviewed, including general recommendations for administration of oral medications through enteral feeding tubes and safe handling of hazardous drugs. Specific recommendations for administration of high-alert medications for patients with chronic diseases are also included.

Self-Nanoemulsified Drug Delivery System of Hydrochlorothiazide for Increasing Dissolution Rate and Diuretic Activity.

Hydrochlorothiazide (HCTZ) is a class IV drug according to the Biopharmaceutical Classification System. This study aimed the development of self-nanoemulsifying drug delivery system (SNEDDS) for HCTZ as an approach to overcome the biopharmaceutical limitations. Pre-formulation screening and ternary phase diagrams were carried out to select the oil phase, the surfactant, and the co-surfactant as the amount of each constituent. The optimized formulations, with reduced amount of surfactant, and composed of medium chain triglycerides, Cremophor EL and Transcutol P did not affect the pH or show drug incompatibilities. The SNEDDS were stabilized by the nanoscale globules and high negative zeta potential. All the physicochemical characterization assays were performed in biorelevant media to better predict the in vivo performance. The enhanced dissolution rate of the SNEDDS reflected in the in vivo diuretic activity, presenting a natriuresis, kaliuresis, and chloriuresis at early stages and an increased volume of total urine compared with HCTZ alone. The designed SNEDDS produced an improvement in the pharmacodynamics due to high dissolution and probable inhibition of intestinal efflux protein by Cremophor EL. The use of SNEDDS demonstrated to be an efficient approach to modulate the absorption of HCTZ and drug therapeutics.

CARACTERIZAÇÃO DOS MEDICAMENTOS ADMINISTRADOS POR SONDA DE NUTRIÇÃO E AS POSSÍVEIS INTERAÇÕES FÁRMACONUTRIÇÃO ENTERAL

Introduction: After many years of its use in clinical practice, nutrition probes are increasingly being used for nutrient intake and drug administration when oral ingestion is impossible. If not properly planned, its use for administration of medications may result in potential complications such as catheter obstruction, reduced drug efficacy, increased adverse effects, and incompatibility of drugs with enteral diet components. Goals: The present study aimed to categorize the drugs prescribed by the nutrition probe, looking for possible interactions between the drugs and the enteral diet of hospitalized patients. Methods: This is a retrospective, quantitative, exploratory work with documentary analysis, taking as prescribing the prescriptions of the patients hospitalized in the emergency ICU. Results: During the study months, 403 patients were hospitalized, and 181 (44.91%) patients met the inclusion criteria. 35 drugs prescribed to be administered by enteral catheter were identified and classified according to the second level of the ATC (Anatomical Therapeutic Chemical) classification, resulting in 22 therapeutic classes. For most drugs, solid dosage forms, corresponding to 86% (n = 30), followed by 14% (n = 5) of liquid dosage forms were prescribed. The predominant pharmaceutical form was the tablet (n = 18). Of the 35 drugs prescribed to be administered by catheter, 10 (28.57%) drugs had potential enteral drug-nutrition interactions. The drugs identified were: atenolol, captopril, carbamazepine, haloperidol, hydrochlorothiazide, aluminum hydroxide, lactulose, levothyroxine, nimodipine, warfarin. Conclusions: Thus, the need for standardization in the administration of probe medications in patients receiving enteral nutrition is noted.

Criteria for choosing an intravenous infusion line intended for multidrug infusion in anaesthesia and intensive care units

ObjectiveThe aims are to identify critical parameters influencing the drug mass flow rate of infusion delivery to patients during multidrug infusion and to discuss their clinical relevance. Data sourcesA review of literature was conducted in January 2016 using Medline, Google Scholar, ScienceDirect, Web of Science and Scopus online databases. Data extractionReferences relating to the accuracy of fluid delivery via gravity-flow intravenous (IV) infusion systems and positive displacement pumps, components of IV administration sets, causes of flow rate variability, potential complications due to flow rate variability, IV therapies especially at low flow rates and drug compatibilities were considered relevant. Data synthesisSeveral parameters impact the delivery of drugs and fluids by IV infusion. Among them are the components of infusion systems that particularly influence the flow rate of medications and fluids being delivered. By their conception, they may generate significant start-up delays and flow rate variability. Performing multidrug infusion requires taking into account two main points: the common dead volume of drugs delivered simultaneously with potential consequences on the accuracy and amount of drug delivery and the prevention of drug incompatibilities and their clinical effects. ConclusionTo prevent the potentially serious effects of flow rate variability on patients, clinicians should receive instruction on the fluid dynamics of an IV administration set and so be able to take steps to minimise flow rate changes during IV therapy.

Potential intravenous drug incompatibilities in a pediatric unit.

ABSTRACTObjective To investigate potential intravenous drug incompatibilities and related risk factors in a pediatric unit.Methods A cross-sectional analytical study conducted in the pediatric unit of a university hospital in Brazil. Data on prescriptions given to children aged 0-15 years from June to October 2014 were collected. Prescriptions that did not include intravenous drugs and prescriptions with incomplete dosage regimen or written in poor handwriting were excluded. Associations between variables and the risk of potential incompatibility were investigated using the Student’s t test and ANOVA; the level of significance was set at 5% (p<0.05). Relative risks were calculated for each drug involved in potential incompatibility with 95% confidence interval.Results A total of 222 children participated in the study; 132 (59.5%) children were male and 118 (53.2%) were aged between 0 and 2 years. The mean length of stay was 7.7±2.3 days. Dipyrone, penicillin G and ceftriaxona were the most commonly prescribed drugs. At least one potential incompatibility was detected in about 85% of children (1.2 incompatibility/patient ratio). Most incompatibilities detected fell into the non-tested (93.4%), precipitation (5.5%), turbidity (0.7%) or chemical decomposition (0.4%) categories. The number of drugs and prescription of diazepam, phenytoin, phenobarbital or metronidazole were risk factors for potential incompatibility.Conclusion Most pediatric prescriptions involved potential incompatibilities, with higher prevalence of non-tested incompatibilities. The number of drugs and prescription of diazepam, phenobarbital, phenytoin or metronidazole were risk factors for potential incompatibilities.

Use of к-carrageenan, chitosan and Carbopol 974P in extruded and spheronized pellets that are devoid of MCC

The search for excipients to replace microcrystalline cellulose (MCC) in the production of pellets by extrusion-spheronization in cases of drug incompatibility or the lack of pellet matrix disintegration forms the basis of this study. A combination of к-carrageenan as a spheronization aid, chitosan as a diluent and Carbopol® 974P as a binder in the production of pellets containing no MCC has been investigated using acetaminophen as a model drug. Design of experiments allowed assessment of formulation and processing effects on pellet responses that included size, shape, fines, yield and friability. Statistical analysis revealed that the main factors and some of the two-factor interactions had a significant effect on pellet characteristics. Formulations containing high levels of к-carrageenan required more water to produce a wetted mass with good extrudability and extrudate capable of being spheronized. Although only a low level of Carbopol was used in the formulation, it imparted cohesiveness to the wetted mass as well as the extrudate. Furthermore, it was discovered that Carbopol could act as an extrusion aid, enabling the wetted mass to flow easily through the extruder screen holes without building up heat. Spherical and rugged pellets were produced that met the immediate release criterion.

Drug incompatibilities in the adult intensive care unit of a university hospital.

ObjectivesThis study sought to identify the physical and chemical incompatibilities among the drugs administered intravenously to patients admitted to an adult intensive care unit. We also aimed to establish pharmaceutical guidelines for administering incompatible drugs.MethodsThis cross-sectional, prospective, and quantitative study was conducted from July to September 2015. Drug incompatibilities were identified based on an analysis of the patient prescriptions available in the hospital online management system. A pharmaceutical intervention was performed using the guidelines on the preparation and administration of incompatible drugs. Adherence to those guidelines was subsequently assessed among the nursing staff.ResultsA total of 100 prescriptions were analyzed; 68 were incompatible with the intravenous drugs prescribed. A total of 271 drug incompatibilities were found, averaging 4.0 ± 3.3 incompatibilities per prescription. The most commonly found drug incompatibilities were between midazolam and hydrocortisone (8.9%), between cefepime and midazolam (5.2%), and between hydrocortisone and vancomycin (5.2%). The drugs most commonly involved in incompatibilities were midazolam, hydrocortisone, and vancomycin. The most common incompatibilities occurred when a drug was administered via continuous infusion and another was administered intermittently (50%). Of the 68 prescriptions that led to pharmaceutical guidelines, 45 (66.2%) were fully adhered to by the nursing staff.ConclusionPatients under intensive care were subjected to a high rate of incompatibilities. Drug incompatibilities can be identified and eliminated by the pharmacist on the multidisciplinary team, thereby reducing undesirable effects among patients.

Impact of clinical pharmacist in an Indian Intensive Care Unit.

Background and Objectives:A critically ill patient is treated and reviewed by physicians from different specialties; hence, polypharmacy is a very common. This study was conducted to assess the impact and effectiveness of having a clinical pharmacist in an Indian Intensive Care Unit (ICU). It also evaluates the clinical pharmacist interventions with a focus on optimizing the quality of pharmacotherapy and patient safety.Materials and Methods:The prospective, observational study was carried out in medical and surgical/trauma ICU over a period of 1 year. All detected drug-related problems and interventions were categorized based on the Pharmaceutical Care Network Europe system.Results:During the study period, average monthly census of 1032 patients got treated in the ICUs. A total of 986 pharmaceutical interventions due to drug-related problems were documented, whereof medication errors accounted for 42.6% (n = 420), drug of choice problem 15.4% (n = 152), drug-drug interactions were 15.1% (n = 149), Y-site drug incompatibility was 13.7% (n = 135), drug dosing problems were 4.8% (n = 47), drug duplications reported were 4.6% (n = 45), and adverse drug reactions documented were 3.8% (n = 38). Drug dosing adjustment done by the clinical pharmacist included 140 (11.9%) renal dose, 62 (5.2%) hepatic dose, 17 (1.4%) pediatric dose, and 104 (8.8%) insulin dosing modifications. A total of 577 drug and poison information queries were answered by the clinical pharmacist.Conclusion:Clinical pharmacist as a part of multidisciplinary team in our study was associated with a substantially lower rate of adverse drug event caused by medication errors, drug interactions, and drug incompatibilities.

集中治療室における注射剤配合変化早見表の作成と有用性の評価

In an intensive care unit (ICU), diverse types of injectable drugs are administrated as continuous infusions according to the condition of the patient. Since incompatibilities of injectable drugs can result in loss of efficacy of medications, it is important that pharmacists quickly recommend appropriate administration routes and provide information on compatibility. In this study, we developed a compatibility chart of frequently used continuous infusions in ICU and evaluated its usefulness.The compatibility chart contained information on trade name, pH, pharmaceutical characteristics, and compatibility with other continuous infusions, for 35 injections. Compatibility determinations were based on information in package inserts, interview forms, and other publications. To evaluate the usefulness of the compatibility chart, we administered a questionnaire survey to 67 nurses and 29 physicians working in ICU.The response rate of nurses and physicians was 100% and 65.5%, respectively. Among the questionees, 91.0% of nurses and 36.8% of physicians had used the compatibility chart. Of the questionees who used the chart, 86.9% of nurses and all physicians rated it as “very useful” or “useful.” Many nurses found that use of the compatibility chart shortened the investigation time of compatibility. Furthermore, this chart provided the pharmacists with quick access to compatibility information.These results show that the compatibility chart for injections was useful in preventing injection incompatibilities in ICU.

Design and development of simvastatin gas powered system for controlled release

Simvastatin is a Hypolipidemic used to control elevated cholesterol, or hypercholesterolemia. The primary uses of simvastatin are for the treatment of dyslipidemia and the prevention of cardiovascular disease. Gas powered Floating tablets of Simvastatin were developed by direct compression method using different grades of HPMC, Carbopol, ethyl cellulose, sodium CMC, sodium alginate, mixture of sodium bicarbonate, citric acid anhydrous as gas generating agents, Citric acid was also used as an antioxidant. The results of Pre-compressional parameters were within I.P prescribed limits. The prepared tablets were subjected to post compression analysis for the parameters such as hardness, friability, weight variation, thickness, diameter, drug content, lag time subsequently buoyancy time, and in-vitro dissolution studies. Tablets of all the formulation floated more than 12hrs. The results of in vitro buoyancy time and lag time study revealed that as the concentration of sodium bicarbonate increases there is increase in total buoyancy time and decrease in lag time. The results of dissolution study reveals that, a decrease in release rate of the drug was observed on increasing the polymer ratio and also by increasing the viscosity grades of the polymer. In all the formulations, hardness test indicated good mechanical strength, friability is less than 1%, indicated that tablets had a good mechanical resistance. DSC and FT-IR studies revealed that, there was no incompatibility of the drug with the excipients used. The stability study conducted as per the ICH guidelines and the formulations were found to be stable. From this study, it can be concluded that, the formulation retained for longer periods of time in the stomach and provides controlled release of the drug and may improved bioavailability.

The Fuster-CNIC-Ferrer Cardiovascular Polypill: a polypill for secondary cardiovascular prevention

AbstractDuring the last decade, there has been a tremendous effort to develop different cardiovascular polypills in response to the upsurge in global cardiovascular disease worldwide. The pharmacological development of such a strategy has proven to be extremely complex from a formulation standpoint. Not all drugs are suitable for use in a polypill because of potential drug incompatibilities between them. Candidate agents must be safe, well tolerated, effective, guideline recommended and physiochemically compatible with the other components of the pill.The Fuster-CNIC-Ferrer cardiovascular (CV) polypill has been found to be the first-in-class polypill to be approved and commercialized in Europe and Latinamerican Countries. In this article, we review the pharmacological properties of its three components, including the clinical evidence supporting their use in patients with established cardiovascular disease, their pharmacokinetic properties, adverse effects, drug interactions and contraindications.

In situ incorporation of monodisperse drug nanoparticles into hydrogel scaffolds for hydrophobic drug release

ABSTRACTThe effective and locally sustained delivery of hydrophobic drug with hydrogels as carriers is still a challenge owing to the inherent incompatibility of hydrophilic hydrogel network and hydrophobic drug. One promising approach is to use porous hydrogels to encapsulate and deliver hydrophobic drug in the form of nanoparticles to the disease sites. However, this approach is currently limited by the inability to load concentrated hydrophobic drug nanoparticles into the hydrogels because of the severe nanoparticle aggregation during the loading process. In this article, we firstly designed and fabricated efficient drug nanoparticles embedded hydrogels for hydrophobic drug delivery by incorporating monodisperse silybin (hydrophobic drug for liver protection) nanoparticles into acrylated hyaluronic acid (HA‐AC) based hydrogels through in situ cross‐linking. The silybin nanoparticles embedded hydrogel scaffolds proved to be a good sustained release system with a long period of 36 h. The drug release from this hybrid hydrogels could be modulated by tuning HA‐AC concentration, cross‐linking ratio, chain length of cross‐linker and drug loading amount. The different kinetic models were applied, and it was observed that the release profile of silybin best followed the Hixson‐Crowell model for the release of drug from the hydrogels embedding silybin nanoparticles. It could be envisioned that this process would significantly advance the potential applications of hydrogel scaffolds mediated hydrophobic drug delivery in clinical therapies. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43111.

Improving intravenous drugs administration in ICU and reducing drug incompatibilities: a nurselead interdisciplinary program

Many intravenous (IV) drugs are required for complex and polypathologic critically ill ICU patients management. ICU nurses are daily confronted with drugs preparation and administration (solvent type and volume, infusion rate). They also have to deal with drugs physiochemical incompatibilities (PCI), especially as various IV medications are delivered via a single catheter lumen. PCI may induce a loss of drug efficiency, catheter thrombosis and embolism. Data about drugs PCI in ICU are scarce (1).

An analysis of IV tubing in an intensive care unit. is there room for improvement?

ICU patients often receive more than twice the number of intravenous (IV) drugs compared to non-ICU patients. It is up to the ICU nurse to determine how the IV tubing between the infusion pumps and patient should be arranged, preferably using a minimal number of lumens in order to avoid discomfort and catheter-related infections. This is a complex task which is prone to error and involves combining various disposables, such as IV lines and valves, and checking for drug incompatibilities.

Drug interactions in pain therapy

Pain is one of the most common reasons for consulting a physician. Chronic pain patients often suffer from a variety of comorbidities, such as depression and anxiety and they are therefore often simultaneously treated with more than one drug. The probability of drug interactions increases with every additional drug. A systematic internet and literature search up to February 2015 was carried out. Systematic lists were included. In addition, the drug prescription information sheets were used and an internet search via Pubmed and google.com was carried out for drugs alone and in combination in order to find substance-specific interactions. A differentiation is made between pharmaceutical, pharmacodynamic and pharmacokinetic drug interactions. Pharmaceutical interactions are caused by chemical, physical or physicochemical incompatibility of drugs or adjuvants used. These can even occur outside the body and during concomitant administration via the same route. A pharmacodynamic interaction in pain management is for example the additive sedative effect of opioids and benzodiazepines when taken together. Pharmacokinetic interactions occur during the absorption, distribution, metabolism and in the elimination phases. Many drug interactions can be avoided by careful and continuous evaluation of pharmacotherapy and if necessary its adaptation; however, a sound knowledge of the underlying pharmacological mechanisms and the properties of currently used analgesics is necessary.

Endothelial Cell Toxicity of Vancomycin Infusion Combined with Other Antibiotics.

French guidelines recommend central intravenous (i.v.) infusion for high concentrations of vancomycin, but peripheral intravenous (p.i.v.) infusion is often preferred in intensive care units. Vancomycin infusion has been implicated in cases of phlebitis, with endothelial toxicity depending on the drug concentration and the duration of the infusion. Vancomycin is frequently infused in combination with other i.v. antibiotics through the same administrative Y site, but the local toxicity of such combinations has been poorly evaluated. Such an assessment could improve vancomycin infusion procedures in hospitals. Human umbilical vein endothelial cells (HUVEC) were challenged with clinical doses of vancomycin over 24 h with or without other i.v. antibiotics. Cell death was measured with the alamarBlue test. We observed an excess cellular death rate without any synergistic effect but dependent on the numbers of combined infusions when vancomycin and erythromycin or gentamicin were infused through the same Y site. Incompatibility between vancomycin and piperacillin-tazobactam was not observed in our study, and rinsing the cells between the two antibiotic infusions did not reduce endothelial toxicity. No endothelial toxicity of imipenem-cilastatin was observed when combined with vancomycin. p.i.v. vancomycin infusion in combination with other medications requires new recommendations to prevent phlebitis, including limiting coinfusion on the same line, reducing the infusion rate, and choosing an intermittent infusion method. Further studies need to be carried out to explore other drug combinations in long-term vancomycin p.i.v. therapy so as to gain insight into the mechanisms of drug incompatibility under multidrug infusion conditions.

Synthesis and in vitro Evaluation of Polymeric Prodrug of Ibuprofen with Amino Acid Spacer.

The present work is an agreement with simple and efficient method of improving the therapeutic efficacy of ibuprofen by masking its acidic moiety. It aims to reduce gastrointestinal side effects by controlling the rate, duration and site of release. This is achieved by synthesis and evaluation of polymeric prodrug of ibuprofen with natural polymer sodium alginate. The synthesis was supported by N-protected serine as spacer due to chemical incompatibility of drug and polymer. Synthesized prodrug was characterized for confirmation of said structures. The in-vitro dissolution profile of ibuprofen-alginate prodrug showed that the release of the drug is significantly higher in case of pH 7.2 buffer as compared to ibuprofen, which might be due to ester group adjacent to drug get hydrolyzed. The hydrolysis was found to be with faster rate in alkaline media than that of in acidic media.

Compatibility of medications during multi-infusion therapy: A controlled in vitro study on a multilumen infusion device

ObjectiveDrug incompatibilities can jeopardize the safety and effectiveness of intravenous drug therapies, especially in the field of anaesthesia and intensive care. Patients receive many drugs simultaneously through limited venous accesses. This study was designed to confirm the impact of a multilumen infusion device on the occurrence of known physical drug incompatibilities. Study designIn vitro laboratory work. MethodsTwo infusion devices were studied: a standard single-lumen set and a multilumen infusion access device (Edelvaiss Multiline-8, Doran International). Up to six drugs were infused simultaneously: three acidic solutions of midazolam, amiodarone and dobutamine, and three alkaline solutions of furosemide, pantoprazole and amoxicillin/clavulanate. Saline, Ringer’ solution and 5% dextrose were used as hydration vehicles with an infusion rate initially set at 100mL/h and with stepwise decreases of 10mL/h until precipitation. Two methods were used to highlight physical drug compatibility according to the European Pharmacopoeia: visual inspection of the extension set and an obscured-light sub-visible particle count test of infusions. The lowest infusion rate value for vehicle infusion to satisfy the two tests in all trials is reported for each infusion device. ResultsThe standard set did not satisfy the test in 82% of the assessed drug combinations. The Edelvaiss Multiline-8 was able to prevent the occurrence of drug incompatibilities in 49% of the drug combinations tested. This device is therefore advantageous, especially when simultaneously infusing two or four incompatible drugs. ConclusionsInfusion device characteristics have an impact on physical drug incompatibilities. Our results confirm that the Edelvaiss Multiline-8 device prevents physical drug incompatibilities under specified conditions.

In vitro analysis of overall particulate contamination exposure during multidrug IV therapy: impact of infusion sets.

Drug incompatibilities, recognizable through precipitate, may have clinical consequences for patients, especially during multidrug IV therapies, where vancomycin and piperacillin are present. Drug concentration and infusion set influence the overall particulate contamination of pediatric infusion protocols. The use of multi-lumen infusion sets could prevent such incompatibilities. Our goal was to define and assess a new way to infuse these drugs during leukemia treatment in children. This in vitro study focused on a pediatric multidrug protocol for patients diagnosed with lymphoblastic leukemia and receiving allogeneic transplantation. Different vancomycin concentrations were tested to infuse incompatible drugs simultaneously without any particle formation (optimized multidrug protocol). A dynamic particle count test was used over 24 hr to evaluate the overall particulate contamination of our standard and optimized multidrug protocols, using both a standard and a multi-lumen infusion set. No visible particles were detected on a decreased vancomycin concentration compared to the standard dose. For the optimized multidrug protocol, the use of a multi-lumen infusion set reduced overall particulate contamination by 68%, compared to the standard infusion set (P = 0.002). Large-sized particles were significantly reduced when using the multi-lumen infusion set approximately 60% (P = 0.027) and 90% (P = 0.009) for particle sizes ≥10 μm and 25 μm, respectively. This study demonstrates that a large number of particles can be administered during parenteral multidrug infusion. The choice of drug concentration and/or the type of infusion set may reduce this. Further studies are required to evaluate adverse clinical effects.